This is a competitive renewal application for the Hormones &Metabolism: Cells, Tissues, Animals &Humans established in 1985 under the direction of Dr. R. Suzanne Zukin, Program Director. For the past twenty years this program has provided multi-disciplinary training at the predoctoral and postdoctoral levels for research careers in diabetes (secretion from islets/genetically engineered beta cells, central and peripheral mechanisms of insulin resistance, diabetic complications, human genetics of diabetes and transgenic animal models) and endocrinology/ metabolism (cell signaling, cell-cell communication, and secretory pathway biology). Request is made for continued support of this highly successful program at the level of six pre-doctoral and two postdoctoral trainee positions. Nearly 5.9% of the U.S. population (or 16,000,000 people) have some form of diabetes mellitus. The need for basic and translational research in diabetes and endocrinology/metabolism has intensified. The past several years have witnessed an explosion of knowledge that links signaling at the level of the central nervous system to regulation of metabolism at the behavioral (feeding) and biochemical (regulation of hepatic glucose output) levels. Thus, the existing strengths of the Program in Endocrinology/metabolism and Neuroscience have synergized to provide a rich and integrated training environment at the cutting edge of research in molecular, cellular and clinical endocrinology research. Our research interactions and the joint training of pre-doctoral and postdoctoral students lend themselves to a highly integrated and cohesive program. Specifically, research training is provided in four major areas. These are: i) Regulation of Hormone Biosynthesis and Secretion (from gene expression to protein processing) (Carrasco, Fricker, Shields) ii) Hormone Receptor Expression, Structure, Function and Intracellular Targeting (Backer, Charron, Etgen, Rubin, Stanley, Zukin) iii) Signal Transduction Molecules, Effectors, and Pathways (Backer, Castillo, Etgen, Rubin, Shields, Stanley, Sze, Zukin) iv) Pathways Regulating Body Metabolism and Disturbances in Obesity and Diabetes (Brownlee, Charron, Chua, Etgen, Fricker, Hawkins, Mehler, Schwartz) Predoctoral fellows will carry out research projects under the supervision of one of the participating faculty in consultation with an advisory committee. Postdoctoral trainees (Ph.D.'s and/or M.D.'s) will engage in full-time research at an advanced level for 1 to 3 years in the laboratory of a faculty trainer. Through participation in works-in-progress seminars, research seminars, journal clubs and formal course work and highly collaborative research projects, trainees will intensively interact with other trainees and faculty mentors and develop the skills necessary for independent investigation. The program enables predoctoral and postdoctoral trainees to obtain multidisciplinary training in an area for which our institution has no other training grant support, namely diabetes and endocrinology/metabolism.